Adaptive Immune Response: Humoral and Cell-Mediated Immunity

Adaptive Immune Response

Humoral vs. Cell-Mediated Immunity

The adaptive immune response is divided into two main branches: humoral immunity and cell-mediated immunity. Each branch involves distinct cell types, mechanisms, and outcomes in defending the body against pathogens.

• Humoral Immunity: Mediated by B lymphocytes and antibodies. Effective against extracellular pathogens (e.g., bacteria, viruses in blood).

• Cell-Mediated Immunity: Mediated by T lymphocytes. Effective against intracellular pathogens (e.g., viruses inside cells, some bacteria, cancer cells).

Feature	Humoral Immunity	Cell-Mediated Immunity
Cell Types Involved	B cells, plasma cells	T cells (Helper, Cytotoxic)
Effector Molecules	Antibodies	Cytokines, cytotoxic molecules
Target	Extracellular pathogens	Intracellular pathogens, abnormal cells
Mechanism	Neutralization, opsonization, complement activation	Direct killing, activation of other immune cells
Memory	Memory B cells	Memory T cells

Types of Acquired Immunity

Acquired immunity can be classified based on how it is obtained and whether it is active or passive.

• Naturally Acquired Immunity:

  • Active: Exposure to pathogen, immune response develops (e.g., infection).

  • Passive: Transfer of antibodies from mother to child (e.g., via placenta or breast milk).

• Artificially Acquired Immunity:

  • Active: Vaccination stimulates immune response.

  • Passive: Injection of antibodies (e.g., antiserum).

Antigens (Ag)

Antigens are substances that provoke an immune response. They are typically macromolecules such as proteins, polysaccharides, or lipids found on pathogens.

• Definition: Any substance that can be recognized by the immune system and elicit a response.

• Examples: Bacterial cell wall proteins, viral capsid proteins.

• Characteristics: Usually large, complex molecules; contain specific regions called epitopes or antigenic determinants.

• Autoimmune Diseases: Occur when the immune system mistakenly targets self-antigens.

Haptens

• Definition: Small molecules that are not immunogenic by themselves but can elicit an immune response when attached to a larger carrier.

• Examples: Penicillin (when bound to proteins).

Antigenic Determinants/Epitopes

• Definition: Specific regions of an antigen recognized by antibodies or T cell receptors.

Antibodies (Ab)

Antibodies are proteins produced by B cells that specifically bind to antigens, facilitating their removal.

• Structure: Typical antibody monomer consists of four polypeptide chains (two heavy, two light) linked by disulfide bonds.

• Regions:

  • Variable Region: Provides antigen specificity.

  • Constant Region: Determines antibody class and function.

  • Fc Region: Made up of constant regions of heavy chains; mediates effector functions (e.g., binding to Fc receptors on immune cells).

• Antigen Binding Site: Formed by variable regions of both heavy and light chains; located at the tips of the "Y" shape.

Antibody Class	Function	Valency
IgG	Main antibody in blood; crosses placenta	2
IgM	First antibody produced; pentamer	10
IgA	Found in mucosal areas; dimer	4
IgE	Allergic responses; binds to mast cells	2
IgD	Surface of B cells; function unclear	2

• Results of Ag-Ab Interactions: Neutralization, opsonization, agglutination, complement activation.

Humoral Immunity

Humoral immunity is mediated by B lymphocytes, which produce antibodies to neutralize pathogens.

• B Lymphocytes:

  • Have surface receptors (BCR) after maturation; proteinaceous in nature.

  • Mature in bone marrow.

• Role in Humoral Response:

  • Recognize antigen via BCR (clonal selection).

  • Proliferate (clonal expansion).

  • Differentiation into plasma cells (antibody production) and memory cells (long-lived).

  • Clonal Deletion: Removal of self-reactive B cells to prevent autoimmunity.

• Primary vs. Secondary Humoral Responses:

  • Primary: First exposure, slower, mainly IgM.

  • Secondary: Subsequent exposure, faster, mainly IgG; involves memory cells.

  • Booster Immunization: Enhances secondary response.

• T-Dependent vs. T-Independent Humoral Responses:

  • T-Dependent: Requires help from T helper cells; usually protein antigens.

  • T-Independent: Does not require T cell help; usually polysaccharide antigens.

• Steps in Humoral Response:

  1. Antigen recognition by B cell (BCR).

  2. Clonal selection and expansion.

  3. Differentiation into plasma and memory cells.

  4. Antibody production.

Cell-Mediated Immunity

Cell-mediated immunity is primarily carried out by T lymphocytes, which recognize and respond to infected or abnormal cells.

• Cytokines: Signaling proteins secreted by immune cells; regulate immune responses.

• T Lymphocytes:

  • Compare to B cells: T cells have TCR, mature in thymus, recognize antigen only as Ag-MHC complex.

  • Types:

    • Helper T cells (TH): CD4+; secrete cytokines, activate B cells and other immune cells.

    • Cytotoxic T cells (TC or CTL): CD8+; kill infected or abnormal cells.

• Antigen Recognition: T cells recognize antigen only when presented as Ag-MHC complex.

• CD4+ T Cells: Recognize Ag-MHC II on APCs; differentiate into TH and memory cells; secrete cytokines to help other cells.

• CD8+ T Cells: Recognize Ag-MHC I on target cells; differentiate into TC/CTL and memory cells; secrete cytotoxic molecules to kill target cells.

• Target Cells for TC/CTL: Virus-infected cells, cancer cells, transplanted cells.

MHC (Major Histocompatibility Complex)

• Definition: Cell surface proteins essential for antigen presentation.

• Classes:

  • MHC I: Found on all nucleated cells; presents to CD8+ T cells.

  • MHC II: Found on professional APCs; presents to CD4+ T cells.

• APC Connection: APCs (e.g., dendritic cells, macrophages, B cells) present antigens via MHC II.

Roles of APCs

• Professional APCs: Dendritic cells, macrophages, B cells.

• Function: Process and present antigens to T cells via MHC II.

NK Cells (Natural Killer Cells)

• Definition: Lymphocytes that kill infected or abnormal cells without antigen-specific receptors.

• Surface Receptors: Do not have antigen-specific receptors like T or B cells.

• Secretion: Release cytotoxic molecules (e.g., perforin, granzymes).

Interrelationship of Humoral and Cell-Mediated Immunity

T helper cells (TH) play a central role in linking humoral and cell-mediated immunity. They help activate B cells (humoral response) and cytotoxic T cells (cell-mediated response), especially in T-dependent antigen responses.

• T-Dependent Antigens: Require T helper cell assistance for B cell activation and antibody production.

Example: Vaccines often use T-dependent antigens to stimulate robust, long-lasting immunity.